This project will test the hypothesis that AAV vectors which are capable of transducing non-dividing cells and directing gene expression from independent transcriptional units can transduce anti-HIV genes into primitive self-renewing pluripotent hematopoietic stem cells in a stable fashion. Multivalent AAV vectors encoding various anti-HIV genes will be tested for their ability to confer resistance to HIV-1. Transduction efficiencies, vector integration and HIV-resistance will be evaluated in the differentiated progeny. The long term transcriptional status of AAV vector genomes will be evaluated to determine the fate of genes delivered by AAV vectors. This study is designed to provide information regarding the basic biology of gene transfer with AAV vectors in addition to the anti-viral efficacy, feasibility and safety of gene therapy of hematopoietic stem cells using multivalent AAV vectors.